title: Leptin induces IL-6 expression through OBRl receptor signaling pathway in human synovial fibroblasts.
abstract: BACKGROUND
  Leptin, an adipocyte-secreted hormone that centrally regulates weight control, may exert proinflammatory effects in the joint, depending on the immune response. Leptin is abundantly expressed in osteoarthritis (OA) cartilage and synovium. However, the relationship between leptin and interleukin-6 (IL-6) in OA synovial fibroblasts (OASFs) remains obscure.
  
  
  RESULTS
  Stimulation of OASFs with leptin induced IL-6 expression in a concentration- and time-dependent manner. OASFs expressed the long (OBRl) and short (OBRs) isoforms of the leptin receptor. However, OBRl, but not OBRs, antisense oligonucleotide (AS-ODN) abolished the leptin-mediated increase of IL-6 expression. Transfection with insulin receptor substrate (IRS)-1 siRNA decreased leptin-induced IL-6 production. In addition, pretreatment of cells with PI3K, Akt, or AP-1 inhibitor also inhibited the potentiating action of leptin. Leptin-induced AP-1 activation was inhibited by OBRl, IRS-1, PI3K, or Akt inhibitors and siRNAs.
  
  
  CONCLUSIONS
  Our results showed that leptin activates the OBRl receptor, which in turn activates IRS-1, PI3K, Akt, and AP-1 pathway, leading to up-regulation of IL-6 expression.
authors.affiliation: Department of Orthopedic Surgery, Taichung Hospital, Department of Health Executive Yuan, Taichung, Taiwan ; Department of Nursing, National Taichung University of Science and Technology, Taichung, Taiwan ; School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan ; Graduate Institute of Biotechnology, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Wei-Hung
authors.initials: WH
authors.lastname: Yang
authors.forename: Shan-Chi
authors.initials: SC
authors.lastname: Liu
authors.forename: Chun-Hao
authors.initials: CH
authors.lastname: Tsai
authors.forename: Yi-Chin
authors.initials: YC
authors.lastname: Fong
authors.forename: Shoou-Jyi
authors.initials: SJ
authors.lastname: Wang
authors.forename: Yung-Sen
authors.initials: YS
authors.lastname: Chang
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
mesh_terms: D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism*; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D013583:Synovial Membrane / Q000378:metabolism*; D014162:Transfection
chemical_list: C508600:IL6 protein, human; D055504:Insulin Receptor Substrate Proteins; D015850:Interleukin-6; D020738:Leptin; D034741:RNA, Small Interfering; D054411:Receptors, Leptin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt